假马齿苋 (BM) 传统上因其抗氧化、抗炎和神经保护作用而用于治疗人类疾病。然而，人们对它的抗癌潜力知之甚少。本研究的目的是探索 BM 对抗口腔癌的详细抗癌机制，并确定可能用于癌症治疗的生物活性 BM 组分。我们进行了生物活性引导分馏，并鉴定了水相BM 乙醇提取物 (BM-AF) 的一部分在体外和体内口腔癌模型中均具有有效的抗癌潜力。 BM-AF 抑制 Cal33 和 FaDu 细胞的细胞活力、集落形成、细胞迁移并诱导细胞凋亡。低剂量的 BM-AF 促进线粒体自噬，并且 BM-AF 介导的线粒体自噬是 PARKIN 依赖性的。此外，BM-AF 抑制槟榔碱诱导的 Cal33 细胞中活性氧的产生。此外，BM-AF 通过 Cal33 细胞中的线粒体自噬抑制槟榔碱诱导的 NLR 家族热蛋白结构域 3 (NLRP3) 炎症小体激活。通过 4-硝基喹啉-1-氧化物和槟榔碱诱导的口腔癌模型，在 C57BL/6J 小鼠中进一步验证了 BM-AF 的体内抗肿瘤作用。 BM-AF 治疗组的肿瘤发生率显着降低。此外，从蛋白质印迹和免疫组织化学分析获得的数据显示，与未治疗的荷瘤小鼠相比，BM-AF治疗的小鼠的舌组织中细胞凋亡标记物的表达增加，而炎性体标记物的表达减少。在体外和体内口腔癌模型中，通过诱导细胞凋亡和线粒体自噬依赖性抑制 NLRP3 炎性体激活，表现出有效的抗癌活性。此外，我们还研究了这种植物提取物中的细胞凋亡和线粒体自噬诱导化合物，对口腔癌细胞具有抗癌活性。版权所有 © 2023 Elsevier GmbH。版权所有。

Bacopa monnieri (BM) is traditionally used in human diseases for its antioxidant, anti-inflammatory and neuroprotective effects. However, its anticancer potential has been poorly understood.The aim of this study was to explore the detailed anticancer mechanism of BM against oral cancer and to identify the bioactive BM fraction for possible cancer therapeutics.We performed bioactivity-guided fractionation and identified that the aqueous fraction of the ethanolic extract of BM (BM-AF) had a potent anticancer potential in both in vitro and in vivo oral cancer models. BM-AF inhibited cell viability, colony formation, cell migration and induced apoptotic cell death in Cal33 and FaDu cells. BM-AF at low doses promoted mitophagy and BM-AF mediated mitophagy was PARKIN dependent. In addition, BM-AF inhibited arecoline induced reactive oxygen species production in Cal33 cells. Moreover, BM-AF supressed arecoline-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation through mitophagy in Cal33 cells. The in vivo antitumor effect of BM-AF was further validated in C57BL/6J mice through a 4-nitroquinolin-1-oxide and arecoline-induced oral cancer model. The tumor incidence was significantly reduced in the BM-AF treated group. Further, data obtained from western blot and immunohistochemistry analysis showed increased expression of apoptotic markers and decreased expression of inflammasome markers in the tongue tissue obtained from BM-AF treated mice in comparison with the non-treated tumor bearing mice.In conclusion, BM-AF exhibited potent anticancer activity through apoptosis induction and mitophagy-dependent inhibition of NLRP3 inflammasome activation in both in vitro and in vivo oral cancer models. Moreover, we have investigated apoptosis and mitophagy-inducing compounds from this plant extract having anticancer activity against oral cancer cells.Copyright © 2023 Elsevier GmbH. All rights reserved.